Bone resorption versus estrogen loss following oophorectomy and menopause

OBJECTIVES: To investigate if menopause and oophorectomy may represent different risk factors for bone resorption/loss. METHODS: The urinary levels of pyridinoline (Pyr) and deoxypyridinoline (D-pyr), the serum levels of type I carboxy-terminal pyridinoline cross-linked telopeptide (ICTP), and lumbar bone mineral density (BMD), were compared in 80 Japanese women after menopause or oophorectomy. These women were divided into four groups of 20 women each as follows: early postmenopausal stage (early physiologic menopause < 3 years before study entry); late postmenopausal stage (physiologic menopause > or = 3 years before study entry); early postoophorectomy stage (oophorectomy < or = 03 years before study entry); or late oophorectomy stage (oophorectomy > 3 years before study entry). RESULTS: Lumbar BMD was significantly lower in the late groups compared to their respective early groups and was lowest in the late postoophorectomy group. The ratio of D-pyr/creatinine (Cr) was not significantly different among the four groups. The ratio of Pyr/Cr was significantly higher in the early postoophorectomy subjects compared with either late group. The serum level of ICTP was significantly higher in the early postoophorectomy group compared to all other groups. CONCLUSIONS: These findings suggest that serum ICTP may be useful in detecting changes in bone resorption after oophorectomy and that women are at greater risk for bone resorption after oophorectomy than after physiologic menopause, although this difference appears to diminish with time.     

Immunohistochemical analysis of thymidylate synthase, p16(INK4a), cyclin-dependent kinase 4 and cyclin D1 in colorectal cancers receiving preoperative chemotherapy: significance of p16(INK4a)-mediated cellular arrest as an indicator of chemosensitivity to 5-fluorouracil

High expression of thymidylate synthase (TS) is allegedly associated with the chemoresistance to 5-fluorouracil (5-FU) in colorectal cancers. However, low TS expression does not necessarily imply chemosensitivity. Inactivation of p16(INK4a) correlates with poor prognosis in various cancers. We immunohistochemically evaluated the relationship between the expression of TS, p16(INK4a), CDK4 and cyclin D1 and the effect of 5-FU-based chemotherapy in colorectal cancers. After antigen retrieval, immunoperoxidase staining was performed on the paraffin-embedded, biopsy and surgical specimens of 37 advanced colorectal cancers preoperatively treated with peroral administration of 5-FU derivatives. As a control group, 31 colorectal cancers without preoperative treatment were analyzed. High TS expression was found in 23 (74%) of 31 tumors resected from histological non-responders and in 19 (61%) of 31 controls but in none of six responders. High p16(INK4a) expression was seen in 83% of the responders, 52% of the non-responders and 32% of the controls. The TS-low/p16(INK4a)-high phenotype was noted in 83% of the responders, but only in 3% of the non-responders (P = 0.0001). Induction of p16(INK4a) expression after chemotherapy was predominantly seen in the responders. Neither CDK4 nor cyclin D1 expression was related to the chemotherapeutic effects. In conclusion, the combination of low expression of TS and induction of p16(INK4a) after chemotherapy can be important indicators of the sensitivity to 5-FU-based chemotherapy in colorectal cancers.     

Memory impairment associated with a dysfunction of the hippocampal cholinergic system induced by prenatal and neonatal exposures to bisphenol-A

One of the most common chemicals that behaves as an endocrine disruptor is the compound 4,4′-isopronylidenediphenol, called bisphenol-A. In the previous study, we reported that exposure to bisphenol-A induced the abnormality of dopamine receptor functions in the mouse limbic area, resulting in a supersensitivity of drugs of abuse-induced pharmacological actions. The present study was undertaken to investigate whether prenatal and neonatal exposures to bisphenol-A could alter other behavioral abnormalities such as anxiogenic behavior, motor learning behavior, or memory. In the present study, adult female mice were chronically treated with bisphenol-A-admixed powder food from mating to weaning. All experiments were performed using male pups. Here we found that prenatal and neonatal exposures to bisphenol-A failed to induce anxiogenic effects and motor-learning impairment using the light-dark test, elevated plus maze test, and rota-rod test. On the other hand, we found that prenatal and neonatal exposures to bisphenol-A induced the memory impairment using the step-through passive avoidance test. Immunohistochemical study showed the dramatic reduction in choline acetyltransferase-like immunoreactivity, which is a marker of acetylcholine (ACh) production, in the hippocampus of mice prenatally and neonatally exposed to bisphenol-A. These results suggest that chronic exposures to bisphenol-A could induce the memory impairment associated with the reduction in ACh production in the hippocampus.     

Numerous eosinophilic globules (skeinoid fibers) in a duodenal stromal tumor: An exceptional case showing smooth muscle differentiation

A unique case of duodenal stromal tumor In a 51-year-old man is reported. The tumor histologically showed spindle cell proliferation and numerous eosinophilic globules. Most globules were composed of tangled 45 nm thick fibrils, which were ultrastructurally Identical to 'skelnoid fibers'. The presence of glycogen granules in the tumor cells and the Immunoreactivity for α-smooth muscle actin suggested smooth muscle differentiation. Focal ultrastructural findings also supported the smooth muscle nature of this tumor. There were no immunohistochemical and ultra-structural features indicating neural differentiation. In previous studies, the presence of such 'skeinoid fibers' was suggested to be a histological marker for neural differentiation in gastrointestinal stromal tumor. However, the findings In the present case suggest that numerous 'skeinoid fibers' can be Identified in duodenal stromal tumor with smooth muscle differentiation, although this condition may be rare.     

Specific arrest of spermatogenesis caused by apoptotic cell death in transgenic mice

Background: The c-myc protooncogene has been implicated in the control of cell proliferation, differentiation and/or apoptosis in various cellular systems. However, the role of c-myc in germ cell lineage is largely unknown.
Results: We have produced transgenic mouse lines carrying the rat c-myc protooncogene under the control of human metallothionein promoter (hMT-c-myc). It was found that the male transgenic mice were sterile. In contrast, all of the female transgenic mice were completely fertile and transmitted the transgene to the next generation. However, male transgenic mice from the female transgenic founders were also found to be sterile. This sterility was due to a defect in spermatogenic cell differentiation, since virtually no sperm were seen within the seminiferous tubules or the cauda epididymis. Histological examination revealed that germ cell death occurred approximately 7 days after birth and, consequently, spermatogenesis was arrested at an early stage in meiotic division in the transgenic mice. Moreover, this germ cell death was found to be caused by apoptosis.
Conclusion: We conclude that an excess level of c-myc expression in differentiating spermatogenic cells is responsible for the apoptotic death of germ cell, and that a decrease in c-myc level would be an obligatory step for the completion of normal spermatogenesis.     

Production and characterization of monoclonal antibodies to a pilus colonization factor (colonization factor antigen III) of human enterotoxigenic Escherichia coli

Three monoclonal antibodies (MAbs) to a pilus colonization factor (colonization factor antigen III [CFA/III]) of human enterotoxigenic Escherichia coli (ETEC) were developed and characterized. All of the MAbs isolated belonged to the immunoglobulin G2a subclass. The specificity of these MAbs for CFA/III pili was demonstrated by the immunogold-labeling technique. The presence of more than one epitope in CFA/III pili was suggested. One of the three MAbs appears to recognize a polymeric conformational epitope(s) of CFA/III. CFA/III antigenicity distinct from that of other pilus colonization factors of ETEC was demonstrated by both a bacterial agglutination test and a sandwich enzyme-linked immunosorbent assay using the MAbs. Of the 100 strains of ETEC isolated from persons with traveler's diarrhea, 8% were found to carry CFA/III pili. Two enzyme-linked immunosorbent assay systems which could detect as little as several or 50 ng of CFA/III per ml were developed.     

Hepatoblastoma in an 82-year-old man. An autopsy case report

An autopsy case of adult hepatoblastoma is presented. The patient was an 82-year-old male with chronic hepatitis of 7 years' duration. The liver tumor was detected 6 months before death. Autopsy revealed a large hepatic tumor occupying about 80% of the entire liver. Histologically, the tumor showed typical features of mixed epithelial- and mesenchymal-type hepatoblastoma. The epithelial component consisted of fetal and embryonal cell types. The mesenchymal component showed primitive spindle-shaped cells with various degrees of cellularity. Chondroid areas and a few foci of osteoid formation were also present.     

Malignant meningioma with cartilage and giant cells.

An autopsy case of recurrent and malignant meningioma is reported. This case was originally typical benign transitional meningioma of the falx, however, the histology of the tumor changed to show malignant features during successive recurrences. At autopsy, the tumor revealed findings consistent with malignant meningioma. One of the most interesting features was the presence of cartilage and giant cells in some parts. Immunohistochemistry showed positive immunoreactivity for S-100 protein in some cartilage and giant cells and for cytokeratin in some giant cells. Multidifferential potential of the meningioma cells was suggested in this case.     

Molecular cloning and expression analysis of a macrophage-colony stimulating factor receptor-like gene from rainbow trout, Oncorhynchus mykiss

The M-CSF and its receptor (M-CSFR, CSF-1R or c-fms proto-oncogene) system were initially implicated as essential in mammals for normal monocyte development as well as for pregnancy. To allow a comparison with the M-CSF and M-CSFR system of an oviparous animal, we cloned a M-CSFR-like gene from rainbow trout (Oncorhynchus mykiss). The gene was cloned from a cDNA library of head kidney. It contained an open reading frame encoding 967 amino acids with a predicted size of 109 kDa. The putative amino acid sequence of rainbow trout M-CSFR showed 54% amino acid identity to fugu (Takifugu rubripes) M-CSFR, 52% to zebrafish (Danio rerio) M-CSFR and 40% to mouse (Mus musculus) and human (Homo sapiens) M-CSFR. The M-CSFR-like gene was constitutively expressed in head kidney, kidney, intestine, spleen and blood. The gene was detected especially in the ovary of immature female rainbow trout. These results suggest that a M-CSFR-like receptor may be involved in female reproductive tracts even in an oviparous animal like fish.